1. Field of the Invention
This invention relates to a pharmaceutical composition and method of administering the same to a mammal, which pharmaceutical composition acts to control the weight of the mammal. More specifically, the composition acts to at least suppress appetite, and preferably also acts to induce thermogenesis and inhibit lipogenesis, so as to prevent weight gain and/or facilitate weight loss.
2. Discussion of Related Art
Serotonergic neurons control the release of neurotransmitters as a function of food uptake. It is well established that carbohydrate consumption increases serotonin release whereas protein ingestion does not. Biochemically, dietary starch is degraded to sugar which stimulates the pancreas to release insulin. Insulin, in turn, raises the levels of tryptophan in the brain. Tryptophan is a precursor of serotonin, and serotonin affects the mood. Neuronal signaling in food consumption, thus, provides a feedback mechanism to maintain a balance between protein and carbohydrate ingestion. Serotonin, however, also affects several other loci in the central nervous system which control, for example, sleep, pain sensitivity, libido, satiety center, maintenance of optimal blood pressure and mood. See, for example, Wurtman et al., "Brain Serotonin, Carbohydrate-Craving, Obesity and Depression," Obesity Research, Volume 3, Supplement 4, pages 477S-480S (1995). Thus, obese people tend to binge on carbohydrates, which is a common cause of weight gain. People exposed to stress, people in depression and ex-smokers trying to disabuse themselves of nicotine habituation also have a tendency to gain weight. In short, there is a clinical link between serotonin, dietary habits, obesity and depression. See Wurtman et al., supra.
It has been known to use certain anti-depressants as weight control agents. For example, Prozac.TM. has been known to be used as a weight control agent. However, as well documented, Prozac has several undesirable side effects. It is therefore desired to develop a weight control composition that is free of undesirable side effects.
Hypericum perforatum, also known as St. John's wort, has been known to be used in treatments to remedy depression, anxiety, mania, hypochondriasis and fatigue. See, for example, Murray, "The Healing Power of Herbs," 2.sup.nd Edition, pages 294-301 (1995); Castleman, "The Healing Herbs," pages 321-325 (1991); Harrer et al., "Treatment of Mild/Moderate Depressions With Hypericum," Phytomedicine, Volume 1, pages 3-8 (1994); and De Smet et al., "St. John's wort As An Antidepressant," BMJ London, Aug. 3, 1996. The major active compounds of interest in Hypericum perforatum are hypericin and pseudohypericin. Hypericum perforatum has the effect of inhibiting serotonin uptake by synaptosomes, thereby increasing the amount of serotonin in the system. This increase in the serotonin level contributes to the anti-depressant activity of Hypericum perforatum. See, for example, Perovic et al., "Pharmacological Profile of Hypericum Extract," Drug Research, Volume 45 (II), No. 11, pages 1145-1148 (1995). Hypericum perforatum is often reported to have no notable side effects (Harrer et al., supra), or very minor side effects, such as gastrointestinal symptoms, allergic reactions and/or fatigue (De Smet et al., supra), as well as reduced appetite. Hypericum perforatum has also been reported to result in an increased appetite (Castleman, supra).
Although Hypericum perforatum is known for use as an anti-depressant, it has not been specifically used as an agent for weight control. Serezac.TM. is a commercially available product containing Hypericum perforatum. Serezac is marketed and administered as an anti-depressant.
The majority of commercially available weight control products focus upon only one avenue of weight control, most typically appetite suppression. This avenue seeks to regulate food intake through drug administration directed to one or more systems known to play a role in food digestion. See, for example, Sullivan et al., "Mechanisms of Appetite Modulation By Drugs," Federation Proceedings, Volume 44, No. 1, Part 1, pages 139-144 (1985). Regulation of serotonin level is one such method of appetite suppression.
However, thermogenesis and inhibiting lipogenesis are other avenues of weight control. Thermogenesis is the major mechanism by which the body burns the metabolically active brown fat. Brown fat cells are a part of the sympathetic nervous system, and serve as a locale for the release of norepinephrine, which triggers thermogenesis. Thermogenesis prevents the storage of dietary lipids while also converting stored fat into soluble lipids that are burnt off by the body to generate energy.
Lipogenesis is a process in which excess glucose is converted into fat and stored in adipose tissues throughout the body. Inhibiting this process, for example by binding a material to the enzyme citrate lyase to reduce the production of fat and cholesterol, can act to reduce weight gain and/or induce weight loss.